CROI 2017 Abstract e-Book

Abstract eBook

Poster and Themed Discussion Abstracts

525 PROGRESSION OF LIVER FIBROSIS IN HIV-MONOINFECTED ADULTS WITH ELEVATED TRANSAMINASES Rebecca Krakora 1 , Mary McLaughlin 2 , David E. Kleiner 3 , Nina Kvaratskhelia 1 , Raissa Canales Santos 4 , Colleen Hadigan 2 , Joseph A. Kovacs 1 , Theo Heller 4 , Caryn G. Morse 1 1 NIH, Bethesda, MD, USA, 2 NIAID, Bethesda, MD, USA, 3 NCI, Bethesda, MD, USA, 4 NIDDK, Bethesda, MD, USA Background: High rates of non-alcoholic steatohepatitis (NASH) and fibrosis have been described in HIV-monoinfected populations. However, data on fibrosis progression in this population are limited. We assessed change in liver fibrosis over time by vibration-controlled transient elastography (VCTE) in a cohort of HIV mono-infected individuals with chronic elevations in serum transaminases. Methods: Antiretroviral-treated HIV-infected adults with elevated serum transaminases enrolled in a natural history of liver disease and with at least two VCTE measurements ≥1 year apart were included in this analysis. Liver stiffness was assessed by VCTE (Fibroscan, Echosens, Paris). Clinical and laboratory variables at baseline were collected and associations with fibrosis progression, defined as an increase of ≥1 NASH Clinical Research Network (CRN) fibrosis stage as estimated by VCTE, were examined. Results: Paired VCTE results were available for 42 patients. On baseline liver biopsy, the majority of patients (n=30) had non-alcoholic fatty liver disease (NAFLD), including 23 (55%) with NASH; the remaining had fibrosis without NAFLD (n=2) or non-specific changes, (n=10). Compared with baseline liver biopsy, baseline VCTE had good sensitivity and specificity with an area under the receiver-operating characteristic curve (AUROC) of 90% for detection of any fibrosis (NASH CRN F>0; 95% confidence interval 81-99%). Over a median of 4.8 years (range 1.4-8.6 years), increased liver stiffness consistent with fibrosis progression was seen in 10 (24%) patients, static disease in 25 (59%) and decreased stiffness consistent with fibrosis regression in 7 (17%). No association was seen between fibrosis progression and baseline biopsy findings, transaminase levels, body mass index, or time between measurements. In 15 participants who underwent a second liver biopsy after a median of 4.0 years (range 2.0-8.0 years), fibrosis progression was observed in 3 (20%). Conclusion: Progression of liver fibrosis is frequently seen in HIV-monoinfected adults with persistent transaminase elevations. Further longitudinal study will help to better characterize the natural history of NAFLD and fibrosis in this population and establish if the natural history differs from that of HIV-negative populations. 526 GUT EPITHELIAL DAMAGE, IMMUNE ACTIVATION & LIVER FIBROSIS IN HIV AND HCV INFECTION Michael J. Reid 1 , Yifei Ma 1 , Rebecca Scherzer 1 , Jennifer Price 1 , Audrey French 2 , Michael Plankey 3 , Carl Grunfeld 1 , Phyllis Tien 1 1 Univ of California San Francisco, San Francisco, CA, USA 2 Rush Univ, Chicago, IL, USA, 3 Georgetown Univ, Washington, DC, USA Background: Markers of gut microbial translocation and innate immune activation have been associated with liver fibrosis progression in HIV/HCV-coinfected persons. Yet, few studies have examined the extent to which immune activation is affected by HIV and HCV infection, gut microbial translocation, and liver fibrosis severity. Methods: Stored plasma from 120 HIV+/HCV+, 262 HIV+/HCV-, 72 HIV-/HCV+, and 170 HIV-/HCV- enrolled in the Women’s Interagency HIV Study and the Study of Visceral Adiposity, HIV, and HCV: Biologic Mediators of Steatosis (VAHH) were tested for intestinal fatty acid binding protein (IFABP, a marker of gut epithelial integrity) and soluble CD14 (sCD14, a marker of monocyte activation). Multivariable linear regression was used to evaluate the association of HIV and HCV with IFABP and sCD14 after adjustment for demographic, lifestyle factors, body composition, and the AST to platelet ratio index (APRI, a marker of liver fibrosis). In analysis with sCD14, additional adjustment for IFABP was performed. Results: After adjustment for demographic, lifestyle factors, and body composition, IFABP levels remained 110%, 77%, and 25% higher in the HIV+/HCV+, HIV+/HCV-, and HIV-/ HCV+ compared to uninfected HIV-/HCV- controls (Table). APRI had no effect on the associations of either HIV-infected group (HIV+/HCV+ or HIV+/HCV-) with IFABP, whereas the association of HCV monoinfection (HIV-/HCV+) was slightly attenuated. After adjustment for demographic, lifestyle factors, and body composition, sCD14 levels were 37%, 20%, and 11% higher in the HIV+/HCV+, HIV+/HCV-, and HIV-/HCV+ compared to uninfected HIV-/HCV- controls. Additional adjustment for IFABP modestly attenuated the associations of both HIV-infected groups (HIV+/HCV+ and HIV+/HCV-) but to a much lesser extent in HCV monoinfection (HIV-/HCV+). By contrast, additional adjustment for APRI substantially attenuated the association of both HCV-infected groups (HIV+/HCV+ and HIV-/HCV+); but the attenuation was much less in HIV monoinfection (HIV+/HCV-). Conclusion: HIV monoinfection is strongly associated with higher IFABP and sCD14 levels, HCV monoinfection to a lesser degree, and the contribution of both HIV and HCV infections appears additive. Gut epithelial damage contributes to immune activation in the setting of HIV, whereas liver fibrosis plays a greater role than gut epithelial damage in the setting of HCV. Our findings show that sCD14 is not a specific marker of gut microbial translocation. 527 VERTICALLY HIV/HCV- VS HCV-INFECTED CHILDREN: HCV TREATMENT & PROGRESSION TO FIBROSIS Carolina Fernández McPhee 1 , Talía Sainz 2 , Loreto Hierro 3 , Antoni Noguera-Julian 4 , Maria José Mellado 2 , Marta Montero 5 , María Isabel González-Tomé 6 , Paloma Jara 3 , Carmen Díaz 3 , Maria Luisa Navarro 1 1 Univ Hosp Gregorio Marañon, Madrid, Spain, 2 Hosp La Paz and IdiPAZ, Madrid, Spain, 3 Univ Hosp La Paz, Madrid, Spain, 4 Univ de Barcelona, Barcelona, Spain, 5 Hosp Univ y Politécnico La Fe, Valencia, Spain, 6 Univ Hosp 12 de Octubre, Madrid, Spain Background: Chronic inflammation and activation of the immune system secondary to HIV infection have been suggested to potentially increase progression of HCV infection in co-infected patients. However, studies addressing the evolution to liver fibrosis and treatment response in vertically HIV/HCV co-infected children are scarce. Methods: Retrospective, multicenter cohort study that included vertically HIV/HCV co-infected patients (COP) registered in the Spanish National Cohort of HIV-infected children (CoRISpe) and vertically HCV mono-infected patients (MOP) from a National Hepatology Reference Center, paired by sex and age, up to December 2015. Treatment-related characteristics and outcomes and progression to hepatic fibrosis were described. Advanced fibrosis was defined as liver stiffness ≥9.6kPa by transient elastography or fibrosis knodell score ≥3 by liver biopsy. Results: A total of 142 patients (71 COP and 71 MOP) were included in the study. It was observed that there was no progression to liver fibrosis during childhood and it was after the age of 9 when patients became at risk. At the age of 20, 9/38 (23.7%) COP vs. 3/54 (5.5%) MOP had progressed to advanced fibrosis (p=0.012). Genotype (GT) distribution was as follow: GT1: 50% vs. 88.3%, GT2: 4.5% vs. 1.7%, GT3: 22.7% vs. 6.7% and GT4: 22.7% vs. 3.3% (all p<0.01). A total of 22 (29.7%) COP vs. 52 (70.3%) MOP received treatment against HCV using combined therapy with Peg-IFN/RBV, except 2 COP treated with Peg-IFN/RBV/telaprevir and 1 COP with Peg-IFN/RBV/boceprevir. At treatment initiation, COP were older compared to MOP: 17 years [15.75-19.25] vs.13 [8.25-15] (p<0.001) and HCV-RNA was no different: 5.8 log [5.2-6.6] vs. 5.6 [5-6.1] (p=0.65). COP had a worse hepatic condition: 40% had moderate to advanced fibrosis and 15% cirrhosis vs. 88.6%with no or mild fibrosis in MOP (all p<0.01). The proportion of HCV cured patients was similar in both groups (40.9% COP vs. 42.3%MOP) and although a higher proportion of cured MOP presented a hard to treat genotype, no significant differences were observed when compared to cured COP: 55.5% vs. 86.4%MOP (p=0.15). Conclusion: No hepatic fibrosis was observed in HIV/HCV co-infected and HCV mono-infected patients during childhood. However, over 20% co-infected patients presented liver disease at the age of 20, suggesting that this population may benefit from early treatment of HCV as soon as new drugs are available for children. HCV treatment outcomes with Peg-IFN/RBV were no different between groups. 528 THE ASSOCIATION BETWEEN HCV AND COMORBID CONDITIONS IN 2 LARGE PATIENT COHORTS Sarah E. Rowan 1 , Joshua Durfee 1 , David C. Tabano 2 , Suzanne Dircksen 1 , Edward Havranek 1 , Aimee Truesdale 1 , Arthur Davidson 1 1 Denver Hlth and Hosp Authority, Denver, CO, USA, 2 Kaiser Permanente Colorado, Denver, CO, USA Background: Hepatitis C (HCV) causes high rates of liver-related morbidity and mortality. The association between HCV and other common medical conditions has been less well characterized. Further, variations in these HCV associations across health care institutions based on demographic and clinical characteristics have yet to be fully described. Methods: Electronic medical records of two large integrated health care systems (Denver Health [DH] and Kaiser Permanente Colorado [KP]) were queried to identify all HCV-related testing between January 1, 2008-December 31, 2014. The testing cohorts were stratified by evidence of infection (detectable HCV RNA) versus no HCV infection (no

Poster and Themed Discussion Abstracts

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